Interest in the long-hypothesized association between tuberculosis and cancer has been intensified by laboratory studies demonstrating that tubercle bacilli (i.e. BCG) potentiate host immune responses against cancer challenge. Recent experiments in man suggest that BCG acts not only to evoke non-specific cell-mediated immunity but also to increase host resistance against specific tumors such as melanoma, sarcoma and breast cancer. In view of these findings, a type of natural experiment in cancer prevention is proposed. A large cohort of tuberculosis patients is to be followed prospectively through time to death or survival as of December 31, 1974. The outcome variables of interest are cancer mortality and morbidity. Observed cancer risks will be compared with those of the contemporaneous general population similar in age, sex and race. Additional analyses will focus upon cancer risk according to clinical severity and extent of tuberculosis, with adjustment for smoking habit. Consideration will also be given to the ascertainment of cancer rates among first-degree family members of the tuberculous as a further test of the antitumor immunogenicity of exposure to tuberculosis. The prospective design of the proposed study should be relatively free of biases inherent in earlier efforts. This approach will also make it possible to study the association (if any) between tuberculosis and all types of cancer: those in which it is significantly positive, those in which it is not significantly negative and those in which there is no significant relationship at all. Retrospective studies do not have this capacity. Should a significant relationship between antecedent tuberculosis and cancer be demonstrated in this population and confirmed by additional studies, the findings could ultimately lead to mass BCG or tuberculin vaccination among the young as a cancer preventative. This is obviously speculative at present, but the potential benefit is so great that we believe an epidemiological study of the type proposed is justified.